ABSTRACT/SUMMARY Food Allergy is a serious and sometimes fatal condition affecting 15 million people in the US for which there currently no cure. There are nearly 200,000 ER visits for food induced anaphylaxis and 100-200 food allergy fatalities in the US every year. Allergen avoidance and rescue epinephrine are the only established management but risk of accidental exposure is very high, especially for children. IgE is central to anaphylaxis in food allergy however, a therapeutic strategy targeting IgE production has not been reported. General Nutraceutical Technology LLC (GNT) spun out of Mount Sinai is a biotech startup based in Elmsford, NY dedicated to development of botanical food allergy therapies. We have developed an innovative natural product nanoparticle formulation of berberine encapsulated with heparin and chitosan (NIT-X). In murine models of peanut allergy, we observed profound, selective and lasting abrogation of peanut-specific IgE which importantly was accompanied by reduction in long-lived IgE-plasma cell numbers. We plan to commercialize NIT-X as an oral syrup formulation designed to treat food allergy. Feasibility of NIT-X development will be demonstrated in the 2 specific aims of this Phase 1 SBIR proposal. In Aim# 1, we hypothesize that NIT-X will be effective in a humanized mouse model peanut allergy and concurrent peanut-tree nut allergy in C3H/HeJ mice. In Aim 2 we will determine preclinical bioavailability, pharmacokinetics and tissue distribution. Completion of these Aims will facilitate human clinical trials planned for Phase II studies. Successful development of NIT-X will provide an innovative and effective solution to life-long food allergy for millions of patients. Effective abolition of long-lived antigen specific plasma cells by NIT-X breaks a long-standing barrier in the field of therapeutic medicine for food allergies and holds strong scientific premise.